PROJECT SUMMARY The Severe Acute Respiratory Syndrome-related Coronavirus 2 (SARS-CoV-2)-driven coronavirus disease 2019 (COVID-19) pandemic has fundamentally changed our world, country, community and families. In patients who die of COVID-19, activation of evolutionarily-conserved inflammatory cascades results in massive increases in circulating levels of inflammatory cytokines producing vascular leak, edema of multiple critical organ (lung, kidneys, heart, brain, liver, GI tract), ultimately leading to multi-organ dysfunction including acute respiratory distress syndrome (ARDS). There is lack of deep understanding regarding the risk factors for and biology of COVID-19. The pandemic has also dramatically highlighted the multiple unmet needs in the care for patients with SARS-CoV-2 infection including the lack of validated biomarkers, and of effective FDA?approved pharmacotherapies. Accordingly, this Administrative Supplement seeks to further our understanding through immunophenotyping patients who develop COVID-19. We will provide clinical data and sample collection/processing from a cohort of SARS-CoV2 patients enrolled in Tucson, Arizona. The clinical data and samples will be transmitted to the central cores that are assigned by the Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) study with the overarching objectives to better understand the pathogenesis of COVID-19 disease and to identify immunological pathways that can be used to inform us on how to combat this disease. In Specific Aim 1, we will recruit and provide clinical data (demographics, clinical laboratory test results and imaging results, clinical course) longitudinally from patients hospitalized with COVID- 19 infection to the designated IMPACC cores in order to establish correlation with immune status and disease progression. In Specific Aim 2, we will provide biological specimens (serum, whole blood, PBMCs, nasopharyngeal samples, endotracheal aspirates) from patients hospitalized with COVID-19 infection to the designated cores in order to characterize the immunophenotypes and the immune status and response to infection. This supplement supports the University of Arizona's participation in IMPACC to facilitate screening and enrollment of inpatients with COVID-19. The proposed supplement research is within the scope of parent U19 grant entitled ?Dysfunction of Innate Immunity in Asthma? (1U19AI125357). In summary, the IMPACC study coordinates a national, multi-institution consortium, collecting detailed clinical data and biologic samples from hospitalized COVID-19 infected individuals, with the goal of identifying immune signatures/molecular biomarkers associated with clinical disease course. These data will allow the prioritization of clinical interventions and therapeutic decision making.